Magnetic shell enhancements during magnetic disturbances

Magnetic shell enhancements during magnetic field disturbances from Langmuir probe observations of electron density on Ariel I satellit

Towards Universal Pension Coverage in Mexico

In 2000 only 22% of older people in Mexico received a pension. Then, in 2002, the first non-contributory pension was introduced in Mexico City. Since then 17 of Mexico's 31 states have also introduced social pensions and so has the federal district. The introduction of these non-contributory pensions meant that in 2013 coverage had risen to 88%. This briefing first looks at the situation before social pensions were introduced, it then tracks the rise in coverage and finishes by suggesting some areas for improvement

Non-contributory Pensions: Bolivia and Antigua in an International Context

Includes bibliographyAbstract The author examines the pension systems of Bolivia and Antigua in the context of non-contributory pensions around the world, concluding with policy lessons. Universal pensions available to everyone of eligible age, regardless of income, assets or employment history, have many advantages over targeted pensions. If targeting is desired, it is best done with ex post recovery from other income rather than ex ante means tests. For reasons that are unclear, governments almost always prefer ex ante tests to ex post controls for noncontributory pensions, even though the reverse is true for tax collection. The worst type of old age pension, from the point of view of poverty relief, is a minimum pension tied to a contributory system or to government service, for this excludes the poorest and most vulnerable from benefits. Key words: Bolivia, Antigua and Barbuda, non-contributory pensions, social security, targeting, means tests

Molecular biology and genetics of epilepsy.

Genetic and molecular biological methodologies are being applied to the study of patients with epilepsy at an ever-increasing pace. Accurate classification of epilepsy within large families has allowed identification of genes through linkage analysis and then isolation of gene products. Mutations causing ion channel abnormalities coupled with clinical patterns of focal epilepsy syndromes are beginning to change our thinking about the etiology of recurrent seizures in all patients. Molecular methodology is beginning to have impact on understanding of the mechanisms of actions of drugs used to treat epilepsy and will have an impact on how future treatments are designed. </p

ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors

\ua9 The Author(s) 2024.Purpose: PARP inhibitors (PARPi) are effective in homologous recombination repair (HRR) defective (HRD) cancers. To (re)sensitise HRR proficient (HRP) tumours to PARPi combinations with other drugs are being explored. Our aim was to determine the mechanism underpinning the sensitisation to PARPi by inhibitors of cell cycle checkpoint kinases ATR, CHK1 and WEE1. Experimental design: A panel of HRD and HRP cells (including matched BRCA1 or 2 mutant and corrected pairs) and ovarian cancer ascites cells were used. Rucaparib (PARPi) induced replication stress (RS) and HRR (immunofluorescence microscopy for γH2AX and RAD51 foci, respectively), cell cycle changes (flow cytometry), activation of ATR, CHK1 and WEE1 (Western Blot for pCHK1S345, pCHK1S296 and pCDK1Y15, respectively) and cytotoxicity (colony formation assay) was determined, followed by investigations of the impact on all of these parameters by inhibitors of ATR (VE-821, 1 \ub5M), CHK1 (PF-477736, 50 nM) and WEE1 (MK-1775, 100 nM). Results: Rucaparib induced RS (3 to10-fold), S-phase accumulation (2-fold) and ATR, CHK1 and WEE1 activation (up to 3-fold), and VE-821, PF-477736 and MK-1775 inhibited their targets and abrogated these rucaparib-induced cell cycle changes in HRP and HRD cells. Rucaparib activated HRR in HRP cells only and was (60-1,000x) more cytotoxic to HRD cells. VE-821, PF-477736 and MK-1775 blocked HRR and sensitised HRP but not HRD cells and primary ovarian ascites to rucaparib. Conclusions: Our data indicate that, rather than acting via abrogation of cell cycle checkpoints, ATR, CHK1 and WEE1 inhibitors cause an HRD phenotype and hence “induced synthetic lethality” with PARPi

Natural antioxidants may prevent posttraumatic epilepsy: a proposal based on experimental animal studies.

Head injury or hemorrhagic cortical infarction results in extravasation of blood and breakdown of red blood cells and hemoglobin. Iron liberated from hemoglobin, and hemoglobin itself, are associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS have been demonstrated to be involved in the mechanism of seizures induced by iron ions in the rat brain, an experimental animal model for posttraumatic epilepsy (PTE). ROS are responsible for the induction for peroxidation of neural lipids, i.e., an injury of neuronal membranes, and also could induce disorders in the excitatory and inhibitory neurotransmitters. Antioxidants, such as a phosphate diester of vitamin E and C (EPC-K1) and antiepileptic zonisamide, have been known to prevent the epileptogenic focus formation, or to attenuate seizure activities in the iron-injected rat brain. Natural antioxidants, such as alpha-tocopherol, and condensed tannins, including (-)-epigallocatechin and (-)-epigallocatechin-3-O-gallate, adenosine and its derivative, melatonin, uyaku (Lindera Strychnifolia), fermented papaya preparations, Gastrodia elata BI., and Guilingji, have been demonstrated to scavenge ROS and/or RNS and to be prophylactic for the occurrence of epileptic discharge in the iron-injected rat brain.</p

Holonomy groups and W-symmetries

Irreducible sigma models, i.e. those for which the partition function does not factorise, are defined on Riemannian spaces with irreducible holonomy groups. These special geometries are characterised by the existence of covariantly constant forms which in turn give rise to symmetries of the supersymmetric sigma model actions. The Poisson bracket algebra of the corresponding currents is a W-algebra. Extended supersymmetries arise as special cases.Comment: pages 2